A Phase IV, Open-Label Study Evaluating the Use of Triple-Combination Therapy With Minocycline HCl Extended-Release Tablets, a Topical Antibiotic/Retinoid Preparation and Benzoyl Peroxide in Patients With Moderate to Severe Acne Vulgaris

June 2013 | Volume 12 | Issue 6 | Original Article | 619 | Copyright © June 2013

Andrea L. Zaenglein MD,a Ava Shamban MD,b Guy Webster MD PhD,c James Del Rosso DO FAOCD,d Jeffrey S. Dover MD FRCPC,e Leonard Swinyer MD,f Linda Stein MD,g Xiaoming Lin MS RN,h Zoe Draelos MD,i Michael Gold MD,j and Diane Thiboutot MDa

aPenn State College of Medicine/Hershey Medical Center, Department of Dermatology, Hershey, PA
bLaser Institute for Dermatology, Santa Monica, CA
cWebster Dermatology, Hockessin, DE
dLas Vegas Skin and Cancer Clinics, Ltd, Henderson, NV
eSkin Care Physicians, Chestnut Hill, MA
fDermatology Research Center, Salt Lake City, UT
gHenry Ford Hospital, Detroit, MI
hMedicis, a Division of Valeant Pharmaceuticals, Scottsdale, AZ
iDermatology Consulting Services, High Point, NC
jTennessee Clinical Research Center, Nashville, TN

Abstract
BACKGROUND: Moderate to severe acne vulgaris is often treated with a combination of an oral antibiotic, topical antibiotic/retinoid, and benzoyl peroxide (BP), but data are limited on the efficacy of this and other combination regimens that incorporate both oral and topical therapies.
METHODS: Patients were required to be aged 12–30 years with moderate to severe acne (grades 3–4 acne on the Investigator's Global Assessment [IGA]) and deemed potential candidates for treatment with isotretinoin. Enrolled patients were given triple-combination therapy, defined in this study as oral minocycline HCl extended release 1 mg/kg QD, 6% BP foaming cloths used QD, and clindamycin phosphate 1.2%/tretinoin 0.025% gel applied QD, and were evaluated at baseline and weeks 2, 4, 8, and 12.
RESULTS: A total of 97 patients were enrolled in the study. At week 12, 89% of patients had at least a one-grade improvement from baseline IGA and 96% had at least a one-grade improvement from baseline Global Aesthetic Improvement Scale score. Mean±SD in- flammatory, non-inflammatory, and total lesion counts decreased from baseline by 61.8%±38.3%, 48.8%±34.5%, and 56.5%±29.9%, respectively. The percentage of patients evaluated as candidates for isotretinoin by independent photographic review was 77% (69/90) at baseline and only 16% (14/90) at week 12. Treatment-related adverse events (AEs) occurred in eight of 97 (8%) patients. Triplecombination therapy was not associated with any serious AEs or AEs leading to discontinuation.
CONCLUSION: Triple-combination therapy was well tolerated and substantially reduced facial acne lesion counts, with 84% of patients judged to no longer be candidates for isotretinoin therapy by study end. These data support the clinical observation that a triple-combination regimen incorporating oral minocycline (dosed by patient weight), BP foaming cloths 6% QD, and clindamycin phosphate 1.2%/ tretinoin 0.025% gel QD can substantially improve moderate to severe acne vulgaris.

J Drugs Dermatol. 2013;12(6):619-625.

INTRODUCTION

Acne vulgaris is a common cutaneous disorder affecting approximately 70% of adolescents and about 50% of adults.1,2 The prevalence of moderate to severe acne ranges from 14%–49% in adolescent populations worldwide.3 Effective management of more severe cases of acne involves use of a therapeutic regimen that targets as many pathogenic mechanisms as possible.4 To achieve this, triple-combination therapy regimens employing an oral antibiotic, topical retinoid, and topical antimicrobial are widely recommended for initial treatment of moderate to severe acne.5
In patients with severe nodular acne, oral isotretinoin is indicated.5 However, oral isotretinoin may also be considered for use in moderate to severe cases of acne that are refractory to combination therapy with a topical retinoid, oral antibiotic, and benzoyl peroxide (BP) with or without a topical antibiotic (ie, clindamycin).6-8 Isotretinoin is the only medication that targets all of the known pathophysiologic factors involved in acne.6 However, isotretinoin is associated with potentially serious systemic adverse events (AEs), especially tetratogenicity if administered during pregnancy, and is highly regulated, requiring close monitoring and frequent visits.6,9,10